It is planned to prepare a number of carbon-linked "C" nucleoside analogs of nicotinamide riboside. Several of these nucleosides will be directly related to NSC 286193 2-Beta-D-ribofuranosylthiazole-4-carboxamide which has shown significant antitumor activity against leukemia P388 and Lewis lung carcinoma in mice. It is proposed to prepare the corresponding thiadiazole nucleoside, 6, the oxazole nucleoside, 7, and the imidazole analog, 20. The synthesis of certain "C" nucleoside analogs of nicotinamide riboside with a six-membered ring is planned via 2,3,5-tri-0-benzoyl-1-cyano-Beta-ribofuranose, 13. Thus the nucleoside 2-Beta-D-ribofuranosyl-pyrimidine-4-carboxamide, 5, and 2-Beta-D-ribofuranosyl 1,3,5,-triazine-4-carboxamide, 40, and 3-Beta-D-ribofuranosyl-1,2,4,-triazine-5-carboxamide, 41, will be prepared via requisite ring closure procedures. Since it has recently been shown that NSC 286193 forms an NAD analog in vivo, it is postulated that such an NAD analog, 3, may act as an antitumor agent by inhibiting ADP ribosylation of the proliferating tumor cell. This appears rather likely since poly ADPR synthetase is known to play a regulatory role in fetal expression and is increased up to 20 times the normal enzymatic activity in certain tumor cells. Several of these new "C" nucleosides will be converted to the 5'-phosphate and then condensed with AMP to give the NAD analogs 43, 44 and 45. These nucleosides and nucleotides will be evaluated at the BYU Cancer Research Center in vitro against leukemia P388 and leukemia L-1210. Compounds active in vitro will be prepared in sufficient quantity for antitumor studies in animals under the auspices of the National Cancer Institute.